Follicular dendritic cells control engulfment of apoptotic bodies by secreting Mfge8.

Animals; Antibodies/immunology; Antigens, CD45/immunology; Antigens, Surface/genetics; Apoptosis/physiology; B-Lymphocytes/cytology/immunology/physiology; Bone Marrow Transplantation; Crosses, Genetic; DNA Primers; Dendritic Cells/immunology; Dendritic Cells, Follicular/cytology/physiology; In Situ Hybridization; In Situ Nick-End Labeling; Macrophages/immunology; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Milk Proteins/genetics/secretion; RNA/genetics; Receptors, Complement 3d/immunology

Abstract :

[en] The secreted phosphatidylserine-binding protein milk fat globule epidermal growth factor 8 (Mfge8) mediates engulfment of apoptotic germinal center B cells by tingible-body macrophages (TBMphis). Impairment of this process can contribute to autoimmunity. We show that Mfge8 is identical to the mouse follicular dendritic cell (FDC) marker FDC-M1. In bone-marrow chimeras between wild-type and Mfge8(-/-) mice, all splenic Mfge8 was derived from FDCs rather than TBMphis. However, Mfge8(-/-) TBMphis acquired and displayed Mfge8 only when embedded in Mfge8(+/+) stroma, or when situated in lymph nodes draining exogenous recombinant Mfge8. These findings indicate a licensing role for FDCs in TBMphi-mediated removal of excess B cells. Lymphotoxin-deficient mice lacked FDCs and splenic Mfge8, and suffer from autoimmunity similar to Mfge8(-/-) mice. Hence, FDCs facilitate TBMphi-mediated corpse removal, and their malfunction may be involved in autoimmunity.

Disciplines :

Anatomy (cytology, histology, embryology...) & physiology

Author, co-author :

Kranich, Jan

Krautler, Nike Julia

Heinen, Ernst ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie humaine

Polymenidou, Magdalini

Bridel, Claire

Schildknecht, Anita

Huber, Christoph

Kosco-Vilbois, Marie H

Zinkernagel, Rolf

Miele, Gino

Aguzzi, Adriano

Language :

English

Title :

Follicular dendritic cells control engulfment of apoptotic bodies by secreting Mfge8.

Publication date :

2008

Journal title :

Journal of Experimental Medicine

ISSN :

0022-1007

eISSN :

1540-9538

Publisher :

Rockefeller University Press, New York, United States - New York

Volume :

205

Issue :

Pages :

1293-302

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 22 September 2009

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Scopus citations^®

146

Scopus citations^®
without self-citations

133

OpenCitations

141

OpenAlex citations

169

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